For people with paralysis or amputation, neuroprosthetic systems that artificially stimulate muscle contractions using electrical current can assist them regain limb function. However, despite many years of research, this type of prosthesis is not widely used because it leads to rapid muscle fatigue and destitute control.
MIT researchers have developed a fresh approach that they hope will one day provide better muscle control with less fatigue. Instead of using electricity to stimulate muscles, they used featherlight. In a study on mice, researchers showed that this optogenetic technique provided more precise muscle control as well as a dramatic reduction in fatigue.
“It turns out that by using light, through optogenetics, you can control your muscles in a more natural way. “In terms of clinical applications, this type of interface could have very broad applications,” says Hugh Herr, professor of media arts and sciences and co-director of the John Paul II Bionics Center. K. Lisa Yang at MIT and an associate member of the MIT McGovern Institute for Brain Research.
Optogenetics is a method of genetically engineering cells to express light-sensitive proteins, which allows researchers to control the activity of these cells by exposing them to featherlight. This approach is not currently possible in humans, but Herr, MIT graduate student Guillermo Herrera-Arcos, and their collaborators at the K. Lisa Yang Bionics Center are currently working on ways to safely and efficiently deliver light-sensitive proteins to human tissue.
Herr is the lead author of the study, which appears today IN . Herrera-Arcos is the lead author of the article.
Optogenetic control
For decades, scientists have been exploring the utilize of functional electrical stimulation (FES) to control muscles in the body. This method involves implanting electrodes that stimulate nerve fibers, causing muscle contraction. However, this stimulation usually activates the entire muscle at once, which is not the human body’s natural way of controlling muscle contraction.
“Humans have incredible accuracy of control, which is achieved through natural muscle recruitment, where small motor units are recruited, then medium motor units, then large motor units, in that order as the signal strength increases,” Herr says. “In FES, when you artificially stimulate muscles with electricity, the largest units are recruited first. So when you increase the signal, at first you get no strength, and then suddenly you get too much strength.
This high force not only makes it difficult to achieve excellent muscle control, but also wears them out quickly, within five to 10 minutes.
The MIT team wanted to see if they could replace the entire interface with something else. Instead of electrodes, they decided to try controlling muscle contractions with optical molecular machines using optogenetics.
Using mice as an animal model, researchers compared the amount of muscle force they were able to generate using the traditional FES approach to those generated using the optogenetic method. The optogenetic studies used mice that had already been genetically modified to express a light-sensitive protein called channelrhodopsin-2. They implanted a small light source near the tibial nerve, which controls the muscles of the lower leg.
The researchers measured muscle strength as the amount of light stimulation was gradually increased and found that, unlike FES stimulation, optogenetic control resulted in a steady, gradual increase in muscle contraction.
“By changing the optical stimulation delivered to the nerve, we can proportionally, in an almost linear way, control the strength of the muscle. This is similar to the way signals from our brain control our muscles. Because of this, it is easier to control the muscles compared to electrical stimulation,” says Herrera-Arcos.
Resistance to fatigue
Using data from these experiments, the researchers created a mathematical model of optogenetic muscle control. This model relates the amount of featherlight reaching the system with the muscle’s efficiency (the amount of force generated).
This mathematical model allowed researchers to design a closed-loop controller. In this type of system, the controller provides a stimulation signal, and when the muscle contracts, a sensor can detect how much force the muscle is exerting. This information is sent back to the controller, which calculates whether and how much the featherlight stimulation needs to be adjusted to achieve the desired strength.
Using this type of control, researchers found that muscles can be stimulated for over an hour before fatigue occurs, while muscles become fatigued after just 15 minutes using FES stimulation.
One hurdle scientists are currently working on is the safe and sound delivery of light-sensitive proteins to human tissue. Several years ago, Herr’s lab reported that in rats, these proteins can trigger an immune response that inactivates the proteins and can also lead to muscle atrophy and cell death.
“A key goal of the K. Lisa Yang Bionics Center is to solve this problem,” Herr says. “Multi-pronged efforts are underway to design new light-sensitive proteins and strategies to deliver them without triggering an immune response.”
In additional steps toward reaching patients, Herr’s lab is also working on fresh sensors that can be used to measure muscle strength and length, as well as fresh ways to implant a featherlight source. The researchers hope that if the strategy is successful, it will benefit people who have experienced strokes, limb amputations and spinal cord injuries, as well as others with impaired ability to control their limbs.
“This could lead to a minimally invasive strategy that would change the clinical care of people with limb pathologies,” Herr says.
The research was funded by the K. Lisa Yang Center for Bionics at MIT.